Long-term Effects of Highly Active Anti-Retroviral Therapy on HIV-Infected Children

HAART Associated Cardiotoxicity in HIV-Infected Children

This study will use the NIH-sponsored Women and Infants Transmission Study (WITS) and the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2) HIV-infected pediatric cohorts to determine how left ventricular (LV) function (particularly fractional shortening and contractility) and structure (particularly wall thickness and mass) are affected by cumulative intensity of exposure to highly active anti-retroviral therapy (HAART).

Study Overview

• Status: Completed
• Conditions: HIV Infections

Detailed Description

BACKGROUND:

HIV-infected children are often given HAART to reduce HIV-associated disease. The long-term effects and toxicities associated with this chronic therapy in children are unknown, but severe cardiotoxicity has been suggested in animal models.

DESIGN NARRATIVE:

The P2C2 HIV-infected pediatric cohort received non-HAART regimens in various intensities. Yet, this cohort has exhibited persistent and significant depression of LV contractility compared to uninfected children (after 5 years of follow-up). These same echocardiographic measures have proven to be independently predictive of mortality. Most of the children in the WITS HIV-infected pediatric cohort have been exposed to HAART at varying times and at varying regimen intensities. By assessing LV structure and function, with the same echocardiographic protocol in the WITS cohort as was used previously in the P2C2 cohort, the study will be able to determine the incremental effects of HAART and non-HAART regimens on LV structure and function. The study will also test the hypothesis that HAART exposure results in impaired mitochondrial function that results in cardiomyopathy. This will be assessed by comparing the parameters of LV structure and function that define cardiomyopathy to the frequency of mitochondrial DNA mutations in cells from these same patients. A nested-case-control study design of mitochondrial mutations will be used to assess the relationship between HAART, mitochondrial compromise, and LV structure and function. Treatment intensity for both HAART and non-HAART regimens will be captured through a cumulative score based on an existing 8-point ordinal scale. Intensity will be measured at three points in time: 1) in utero; 2) during the first year of life; and 3) after the first year of life. Analysis of the longitudinal echocardiographic and mitochondrial data will provide valuable information about dose intensity and the comparative impact of HAART versus less aggressive drug regimens. It will also provide information on the impact of therapy during different stages of child development. Similar longitudinal data on viral load and duration of HIV will enable the investigators to control for the effects of HIV infection on cardiovascular toxicity. The findings will help determine the need for cardiovascular follow-up, prevention, and therapeutic trials.

• Study Type: Observational
• Enrollment (Actual): 71

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico
    • University of Puerto Rico
• United States
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami Miller School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois - Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21210
      • Clinical Trials and Surveys Corp. (C-TASC)
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • Brooklyn, New York, United States, 11203
      • State University of New York (SUNY)
    • New York, New York, United States, 10027
      • Columbia University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study participants will be children perinatally infected with HIV who were enrolled in the Women and Infants Transmision Study (WITS).

This cohort will be compared to the historical Pediatric Pulmonary and Cardiovacular Complications Study (P2C2 HIV) cohort of perinatally HIV-infected children not exposed to HAART.

Description

Inclusion Criteria:

• HIV-infected children
• Mothers of children understand and are willing to provide informed consent
• Mothers of children are capable of answering in English or with the help of an interpreter

Exclusion Criteria:

• HIV-infected child who is too young (less than 2 years of age) or otherwise unable to undergo an echocardiogram without sedation
• Mothers of children have maternal diabetes or phenylketonuria
• Mothers of children have a recognized Mendelian or chromosomal defect
• Mothers of children are/were actively receiving chemotherapy for cancer during pregnancy
• Mothers of children used lithium carbonate, anticonvulsants, amphetamines, or angiotensin converting enzyme (ACE) inhibitors on a chronic basis

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; Children perinatally infected with HIV with exposure to highly active anti-retroviral therapy (HAART).
2; Children with perinatally acquired HIV infection enrolled on the P2C2 Study, not exposed to HAART therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cardiac systolic function	Measured from 2 years of age to 18 years of age

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: Baylor College of Medicine; National Heart, Lung, and Blood Institute (NHLBI); Columbia University; Boston Children's Hospital; University of Illinois at Chicago; Boston Medical Center; University of Puerto Rico; State University of New York; Clinical Trials & Surveys Corp (C-TASC)
• Investigators: Principal Investigator: Steven E. Lipshultz, MD, University of Miami

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: December 1, 2005
• First Submitted That Met QC Criteria: December 1, 2005
• First Posted (Estimate): December 2, 2005

Study Record Updates

• Last Update Posted (Estimate): March 18, 2014
• Last Update Submitted That Met QC Criteria: March 17, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 1318; R01HL078522 (U.S. NIH Grant/Contract)